Integrated, Transparent Silicon Carbide Electronics and Sensors for Radio Frequency Biomedical Therapy

The integration of micro- and nanoelectronics into or onto biomedical devices can facilitate advanced diagnostics and treatments of digestive disorders, cardiovascular diseases, and cancers. Recent developments in gastrointestinal endoscopy and balloon catheter technologies introduce promising paths for minimally invasive surgeries to treat these diseases. However, current therapeutic endoscopy systems fail to meet requirements in multifunctionality, biocompatibility, and safety, particularly when integrated with bioelectronic devices. Here, we report materials, device designs, and assembly schemes for transparent and stable cubic silicon carbide (3C-SiC)-based bioelectronic systems that facilitate tissue ablation, with the capability for integration onto the tips of endoscopes. The excellent optical transparency of SiC-on-glass (SoG) allows for direct observation of areas of interest, with superior electronic functionalities that enable multiple biological sensing and stimulation capabilities to assist in electrical-based ablation procedures. Experimental studies on phantom, vegetable, and animal tissues demonstrated relatively short treatment times and low electric field required for effective lesion removal using our SoG bioelectronic system. In vivo experiments on an animal model were conducted to explore the versatility of SoG electrodes for peripheral nerve stimulation, showing an exciting possibility for the therapy of neural disorders through electrical excitation. The multifunctional features of SoG integrated devices indicate their high potential for minimally invasive, cost-effective, and outcome-enhanced surgical tools, across a wide range of biomedical applications.


Electrical stability in accelerated hydrolysis test
ITO thin-film resistors (sourced from Sigma Aldrich TM , with the sheet resistance of 8-10 Ω/square) were prepared by sputtering Ti electrodes through a shadow mask and diced into 30×5mm 2 chips. Subsequently, they were soaked in 1X PBS solution at a temperature of 70 °C to validate their long-term stability and feasibility for high temperature RF ablation.
Experimental results revealed that the resistance of ITO increased by approximately 250% after 5 days soaked in PBS at 70 °C, Figure S1(b). This significant change in electrical conductivity of ITO is attributed to a combination of the hydrolysis reaction, the absorption of water molecules, and the diffusion of ions from the biofluid into the film. This is in stark contrast to that of SiC in the soaking test at 96°C, Figure S1

Fabrication process of SiC bioelectronics
The fabrication process for the SiC bioelectronics systems started with the growth process of SiC on a Si wafer with SiC and Si thicknesses of 600 nm and 500 µm, respectively. Figure S2 shows the TEM (a) and SAED images to verify that single crystalline 3C-SiC(100) has been grown. The AMF image indicated an excellent uniformity and smoothness of as grown SiC film on Si, Figure S3. The root-mean-square roughness of approximately 3nm is obtained, and the carrier concentration is measured to be in the range of 5×10 19 cm -3 . The wafer was then bonded to a glass substrate followed by a polishing and chemical wet etching to remove Si carrier wafer. 1 To pattern SiC and contact paths on a new substrate (i.e., glass), first, 1.2 μm-thick positive photoresist was coated on the wafer using a spin coater at a speed of 4000 rpm. This photoresist was then soft baked at 105 °C in 1 min followed by lithography exposure (MLA 150) then patterned in photoresist developer. To prepare for the SiC process, the as-patterned photoresist is hard baked in 3 mins at 120 °C. Next, inductive coupled plasma (ICP) etching was employed to pattern the SiC electrodes and sensors. In the etching process, the chamber pressure was set at 2 mTorr with the plasma power of 120 W. As the average etching rate using HCl was approximately 100 nm/min, the etching process was performed until SiC pattern is completely etched (600 nm). 300 nm thick aluminum layer was deposited using a CVD sputtering machine and then electrodes were formed with photolithography and wet etching processes using Al etchant. Finally, 10 μm polyimide encapsulation was coated then pattern to open the exposed electrode areas while covering the contact path for the electrical isolation.

Temperature sensing calibration
To calibrate the integrated SiC temperature sensor, a enclosed temperature chamber was employed. The chamber temperature was varied from a test range from 20 °C to 80 °C monitored with a K-type thermometer (FLUKE TM 714B) where K-type bead probe was placed closed to the SiC-on-glass chip, Figure S4. Figure S4. Temperature calibration for integrated temperature sensor using an enclosed chamber and K-type thermometer.

Phantom tissue preparation
Prepare the buffer and weigh the agarose gel powder (as per the requirement) 1. Mix agarose powder with PBS solution in a microwavable flask.
2. Dissolve the agar by heating the solution for intervals of 15-20 seconds in a microwave oven.
3. After each interval, remove the flask and gently swirl around to disperse the contents.
The heat interval was used to avoid overboiling the solution since the fast evaporation of buffer can lead to changes in the agar concentration in the gel.

5.
Pour the solution to a petri dish and avoid causing bubbles that can disrupt the gel, then keep the mixed gel at room temperature for 1 hour, wait until completely solidified.
6. Cure the gel in air for 20 mins.

Radio frequency thermal ablation modeling
In the present study, RF thermal ablation was modelled by COMSOL TM Multiphysics, and the obtained results are shown in Figure S5. During the tissue ablation, the temperature distribution at different applied sinusoidal voltage at the middle point of upmost tissue surface presents similar trend, as shown in Figure S5(a). During the initial seconds, there exists a quick temperature rise, then followed by a steady platform. Simulation results showed that evaporation related dissipation had minor impact on tissue ablation. Approximately, scaling law for temperature rise dictates: where κ, σ, S, L, V0, and T0 is thermal conductivity, electrical conductivity, electrode size, electrode spacing, applied potential, and initial temperature, respectively. The related scaling behavior of model parameters at the middle point of upmost tissue surface was shown in Figure   S5

Irreversible electroporation modeling
The irreversible electroporation was also simulated with the electric field distribution shown in Figure S7. During the electroporation, the electric field was excited in dimensional analyses to obtain the scaling law for electric field strength as: Where S, L, and V0 is electrode size, electrode spacing, and applied potential, respectively. The validation of the scaling law for the electric field strength was shown in Figure S8. As such, with constant S/L, the electric field strength changes linearly with V0/L, Figure S8  ITO is a degenerated n-type semiconductors, that exhibits good electrical conductivity, suitable for bioelectronics applications. 2 However, the high electrical conductivity also makes ITO behaving as metallic materials, which is nontrivial to modulate its physical properties through external stimuli such as photoenergy or strain engineering. To make ITO functioning as a semiconducting material, its thickness has to be reduced to an order of 10 nm, which correlates to the maximum depletion width (tens of nm for ITO field effect transistor channels). 3 However, as shown in Figure S1(b), the electrical resistance of ITO is relatively unstable in biofluid environment; therefore thinning down the film thickness will significantly reduce the device lifetime and stability. This drawback hinders the multimodalities of ITO for bioapplications. Si is the mainstream semiconducting materials with well-established fabrication technologies.
However, as Si is not a transparent material, it is not suitable for biomedical devices where realtime observation is required. Two-dimensional materials have attracted significant research interest for a wide range of applications. Their excellent optical transparency places them as a S19 good candidate for bioelectronics electrodes and sensing components that allow optical observation. However, two dimensional materials typically exhibit highly active surface states, posing long-term stability issues when working under biofluid. In contrast, nanothin film SiC on glass can be engineered with an optimal conductivity such as highly doped for bioelectrodes (high current carrying capacity) and low doped for sensing elements (for sensitivity enhancements), along with excellent chemical stability. The fabrication processes for SiC nanothin films are highly compatible with conventional MEMS processes (i.e., dry etching of SiC), making it much more versatile compared to other SiC polytypes (e.g., 4H-, 6H-SiC) or bulk diamond like carbon. Micromachining for these polytypes is typically difficult due to the requirement of etching relatively thick SiC films (e.g., several hundreds of micrometer-thick).
As an example, to form a 4H-SiC diaphragm, a top-down laser ablation method was introduced. 4, 5 However, the surface roughness of 4H-SiC was significantly higher (above 10 µm). Figure S14 highlights the advantages of our SiC-on-glass compared to other transparent counterparts in fabrication, integration, and functionality.